NM_000238.4(KCNH2):c.1882G>A (p.Gly628Ser) AND Long QT syndrome

Clinical significance:Pathogenic (Last evaluated: May 12, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000822422.3

Allele description [Variation Report for NM_000238.4(KCNH2):c.1882G>A (p.Gly628Ser)]

NM_000238.4(KCNH2):c.1882G>A (p.Gly628Ser)

Gene:
KCNH2:potassium voltage-gated channel subfamily H member 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7q36.1
Genomic location:
Preferred name:
NM_000238.4(KCNH2):c.1882G>A (p.Gly628Ser)
HGVS:
  • NC_000007.14:g.150951511C>T
  • NG_008916.1:g.31416G>A
  • NM_000238.4:c.1882G>AMANE SELECT
  • NM_001204798.2:c.862G>A
  • NM_172056.2:c.1882G>A
  • NM_172057.3:c.862G>A
  • NP_000229.1:p.Gly628Ser
  • NP_000229.1:p.Gly628Ser
  • NP_001191727.1:p.Gly288Ser
  • NP_742053.1:p.Gly628Ser
  • NP_742054.1:p.Gly288Ser
  • LRG_288t1:c.1882G>A
  • LRG_288t2:c.1882G>A
  • LRG_288:g.31416G>A
  • LRG_288p1:p.Gly628Ser
  • LRG_288p2:p.Gly628Ser
  • NC_000007.13:g.150648599C>T
  • NM_000238.2:c.1882G>A
  • NM_000238.3:c.1882G>A
  • Q12809:p.Gly628Ser
Protein change:
G288S; GLY628SER
Links:
UniProtKB: Q12809#VAR_008583; OMIM: 152427.0008; dbSNP: rs121912507
NCBI 1000 Genomes Browser:
rs121912507
Molecular consequence:
  • NM_000238.4:c.1882G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001204798.2:c.862G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172056.2:c.1882G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172057.3:c.862G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Long QT syndrome (LQTS)
Identifiers:
MONDO: MONDO:0002442; MeSH: D008133; MedGen: C0023976; OMIM: PS192500

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000963223Invitaecriteria provided, single submitter
Pathogenic
(May 12, 2020)
germlineclinical testing

PubMed (9)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome.

Curran ME, Splawski I, Timothy KW, Vincent GM, Green ED, Keating MT.

Cell. 1995 Mar 10;80(5):795-803.

PubMed [citation]
PMID:
7889573

Long QT syndrome in neonates: conduction disorders associated with HERG mutations and sinus bradycardia with KCNQ1 mutations.

Lupoglazoff JM, Denjoy I, Villain E, Fressart V, Simon F, Bozio A, Berthet M, Benammar N, Hainque B, Guicheney P.

J Am Coll Cardiol. 2004 Mar 3;43(5):826-30.

PubMed [citation]
PMID:
14998624
See all PubMed Citations (9)

Details of each submission

From Invitae, SCV000963223.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (9)

Description

This sequence change replaces glycine with serine at codon 628 of the KCNH2 protein (p.Gly628Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with long QT syndrome including affected individuals where the variant was observed de novo (PMID: 7889573, 14998624, 22949429, 17088455, 16922724). ClinVar contains an entry for this variant (Variation ID: 14427). This variant has been reported to affect KCNH2 protein function (PMID: 9694858, 23303164, 8700910). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Dec 4, 2021

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